7JXS

Crystal Structure Human Immunodeficiency Virus-1 Matrix protein Mutant Q63R Crystal Form 2

7JXS の概要

• エントリーDOI: 10.2210/pdb7jxs/pdb
• 分子名称: Matrix protein, DODECAETHYLENE GLYCOL, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: hiv-1, gag, structural protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95500.09

構造登録者

Green, T.J.,Eastep, G.N.,Ghanam, R.H.,Saad, J.S. (登録日: 2020-08-27, 公開日: 2021-04-14, 最終更新日: 2023-10-18)

主引用文献

Eastep, G.N.,Ghanam, R.H.,Green, T.J.,Saad, J.S.
Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation.
J.Biol.Chem., 296:100321-100321, 2021

PubMed Abstract: During the late phase of HIV-1 infection, viral Gag polyproteins are targeted to the plasma membrane (PM) for assembly. Gag localization at the PM is a prerequisite for the incorporation of the envelope protein (Env) into budding particles. Gag assembly and Env incorporation are mediated by the N-terminal myristoylated matrix (MA) domain of Gag. Nonconservative mutations in the trimer interface of MA (A45E, T70R, and L75G) were found to impair Env incorporation and infectivity, leading to the hypothesis that MA trimerization is an obligatory step for Env incorporation. Conversely, Env incorporation can be rescued by a compensatory mutation in the MA trimer interface (Q63R). The impact of these MA mutations on the structure and trimerization properties of MA is not known. In this study, we employed NMR spectroscopy, X-ray crystallography, and sedimentation techniques to characterize the structure and trimerization properties of HIV-1 MA A45E, Q63R, T70R, and L75G mutant proteins. NMR data revealed that these point mutations did not alter the overall structure and folding of MA but caused minor structural perturbations in the trimer interface. Analytical ultracentrifugation data indicated that mutations had a minimal effect on the MA monomer-trimer equilibrium. The high-resolution X-ray structure of the unmyristoylated MA Q63R protein revealed hydrogen bonding between the side chains of adjacent Arg-63 and Ser-67 on neighboring MA molecules, providing the first structural evidence for an additional intermolecular interaction in the trimer interface. These findings advance our knowledge of the interplay of MA trimerization and Env incorporation into HIV-1 particles.

PubMed: 33485964
DOI: 10.1016/j.jbc.2021.100321

実験手法

X-RAY DIFFRACTION (2.35 Å)